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Engineering the Bio-Nano Interface Using a Multi-Functional Polymer Coating

Title: Engineering the Bio-Nano Interface Using a Multi-Functional Polymer Coating.
Name(s): Wang, Wentao, author
Mattoussi, Hedi, professor directing dissertation
Tang, Hengli, university representative
Schlenoff, Joseph B., committee member
Knappenberger, Kenneth L., committee member
Florida State University, degree granting institution
College of Arts and Sciences, degree granting college
Department of Chemistry and Biochemistry, degree granting department
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2016
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource (237 pages)
Language(s): English
Abstract/Description: Interfacing inorganic nanoparticles with biological systems to develop a variety of novel imaging, sensing and diagnostic tools has generated great interest and much activity over the past two decades. However, the effectiveness of this approach hinges on the ability to prepare water dispersible nanoparticles, with compact size and long term colloidal stability in biological environments, and the development of controlled conjugation to various biomolecules. The primary focus of this dissertation is the design and synthesis, characterization and use of a series of new multidentate and multifunctional coordinating polymers as ligands that render various inorganic nanocrystals water soluble, with emphasis on: i) how to improve the colloidal stability, ii) how to design compact coating, iii) how to engineer the nanoparticle surface with tunable functionalities to achieve bioconjugation, and iv) how to develop the resulting nanoprobes into biological sensing and imaging. This dissertation is organized as follows: In Chapter 1 we introduce the basic physical properties of quantum dots (QDs), gold nanocrystals and magnetic nanocrystals along with brief description of their syntheses. We then provide an overview of surface functionalization strategies and recent progress in the ligand chemistry, followed by highlights of a few conjugation approaches applied to nanoparticles in biology. We then discuss modulation of the optical and spectroscopic properties of QDs via energy and charge transfer interactions. We conclude by presenting a few related examples on the incorporation of QD-conjugates into sensor design and intracellular imaging. In Chapter 2, we report the design of a series of multifunctional polymers as ligands for surface engineering of QDs and facilitating their use in bioconjugation. This Chapter includes three sections: • First, we introduce a novel PEGylated polymer that combines the synergies of metal-chelation promoted by lipoic acid and imidazole groups, as effective coating for the surface functionalization of QDs; one of the goals was to address the problems associated with thiol oxidation and weak imidazole affinity. We detail the ligand synthesis via the highly efficient, one-step nucleophilic addition reaction between a central poly(isobutylene-alt-maleic anhydride) chain (as a scaffold) and several distinct but complementary amine-presenting functionalities. We then demonstrate the use of in situ phase transfer of hydrophobic QDs into water mediated by a mild photoligation strategy under borohydride-free conditions. Ligation with these polymers provides QDs with excellent colloidal stability over a wide range of conditions; this improves on what has been reached using coating with ligands presenting lower coordination of thiol only or imidazole only. • Second, to minimize the hydrodynamic radius of the QDs without sacrificing aqueous solubility, a set of polymer ligands appended with zwitterion and imidazole motifs have been synthesized applied for the surface engineering of QDs. By using zwitterion as the hydrophilic block, this design provides QDs with a thin coating and very compact overall dimension; this has, for example, allowed the self-assembly of QDs with polyhistidine-tagged proteins via metal−histidine coordination. We further show that the assembled QD-dopamine conjugates can be used to detect iron ions and amino acid cysteine through charge-transfer interactions. Finally, we demonstrate that QDs ligand exchanged with folic acid-functionalized ligand are capable of targeting cancerous cells. • Third, modulation of the nanoparticle’s interaction with biological systems requires access to an effective conjugation of these materials with bioactive targets in a controlled manner. To fulfill this goal, we have developed several zwitterion-based multifunctional ligands presenting tunable functional groups, including carboxyl, amine, azide and biotin. This has allowed conjugation of the QDs to biomolecules via bio-orthogonal coupling chemistries, including (1) amine-isothiocyanate reaction; (2) biotin-streptavidin self-assembly; (3) copper-free click chemistry. The resulted QD-bioconjugates have been tested in sensor design and for cell imaging. We also find that the efficiency of polyhistidine-mediated metal coordination is not only determined by the ligand lateral extension but also greatly influenced by the nature of metal coordination on the QDs. In Chapter 3, we have applied the various multi-coordinating and multi-reactive polymers, in particular, those presenting lipoic acid and PEG for the functionalization of gold nanoparticles and nanorods. Gold nanocrystals coated with this polymer exhibit excellent long-term colloidal stability over a broad range of conditions, and furthermore prevent the formation of protein corona. This was verified using dynamic light scattering measurements combined with agarose gel electrophoresis. The diffusion properties of polymer-coated nanocrystals were further characterized using dynamic light scattering; this has yielded valuable information on the nature of the interparticle interactions in biological media. In Chapter 4, an additional set of modular ligands were synthesized and applied for the surface modification of iron oxide nanoparticles. These ligands feature several dopamines for tight binding on iron oxide nanoparticle surface, a short PEG for water solubility and reactive groups (amine, carboxyl, azide and thiol) for bioconjugation. Nanoparticles functionalized with these polymers show extended stability in biologically relevant conditions and little to no cytotoxicity. We demonstrate that covalent attachment of dye enables producing luminescent probe for cell imaging. A summary of the major contributions assembled in this dissertation along with a discussion of the future outlook is provided in Chapter 5.
Identifier: FSU_FA2016_Wang_fsu_0071E_13497 (IID)
Submitted Note: A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the Doctor of Philosophy.
Degree Awarded: Fall Semester 2016.
Date of Defense: September 21, 2016.
Keywords: Bioconjugation, Inorganic Nanocrytsals, Ligand Chemistries, Quantum Dots, Sensing and Imaging, Surface Functionalization
Bibliography Note: Includes bibliographical references.
Advisory Committee: Hedi Mattoussi, Professor Directing Dissertation; Hengli Tang, University Representative; Joseph B. Schlenoff, Committee Member; Kenneth L. Knappenberger, Committee Member.
Subject(s): Chemistry
Chemistry, Physical and theoretical
Persistent Link to This Record:
Host Institution: FSU

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Wang, W. (2016). Engineering the Bio-Nano Interface Using a Multi-Functional Polymer Coating. Retrieved from